Chi-Sin Changchien

Clinical and Histological Events Preceding Hepatitis B e Antigen Seroconversion in Chronic Type B Hepatitis

A 60-mo longitudinal study has been undertaken in 99 HBeAg-positive patients with clinicopathologically verified chronic hepatitis. Hepatitis B e antigen clearance occurred in 30 patients at a rate of approximately 17% per year. A phenomenon of abrupt elevation of serum glutamic pyruvic transaminase (greater than 300 IU/L) with histological changes compatible with chronic lobular hepatitis was observed in 13 of 20 patients (65%) preceding spontaneous HBeAg clearance. In contrast, 8 of 10 patients on immunosuppressive or antiviral therapy, or both, had uneventful HBeAg clearance. It was concluded that HBeAg clearance can occur in patients with varying immunologic status. The mechanism responsible for HBeAg clearance awaits further study.

Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis

Background. We aimed to evaluate the validity of ultrasonography (US) in the diagnosis of cirrhosis in patients with chronic hepatitis B virus (HBV) or C virus (HCV) infection. Methods: A total of 210 patients, 67 with chronic HBV and 143 with HCV infection, were evaluated for the cirrhotic status of liver by both needle biopsy and US. According to the pathological findings, a fibrosis score 4 on the histology activity index was the gold standard for the diagnosis of cirrhosis. A US scoring system consisting of liver surface, parenchyma, vascular structure, and splenic size was used to describe the severity of hepatic parenchymal damage. Results: Cirrhosis was found in 27 (40%) of the 67 HBV patients and in 51 (36%) of the 143 HCV patients pathologically. The mean fibrosis scores were 0.95, 1.24, 2.35, 2.95, 3.8 and 3.7 in patients with US scores of 4, 5, 6, 7, 8, and 9 or more, respectively. The US scores were significantly correlated with the hepatic fibrosis scores (P < 0.05). Based on the receiver operating characteristic (ROC) curve, a US score of 7 was the best cutoff point for the prediction of HBV-related cirrhosis, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 77.8%, 92.5%, 87.5%, 86.0%, and 86.6%, respectively. In HCV-related cirrhosis, a US score of 6 provided results of 82.4%, 70.7%, 60.9%, 87.8%, and 74.8%, respectively. The specificity, positive predictive value, and accuracy were significantly higher in patients with HBV than in those with HCV infection (P = 0.012, P = 0.032, and P = 0.079, respectively). Conclusions: Cirrhosis can be predicted well by US, especially in patients with HBV infection.

The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma – Survival analysis of 3892 patients

The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification and treatment allocation for hepatocellular carcinoma (HCC). We conducted this retrospective study to assess the efficacy of different treatment options for patients with initial HCC diagnosis. Survival rate and median survival times associated with different treatment options in each stage of BCLC classification were compared using the Kaplan-Meier method and log-rank test. A total of 3892 patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at 5 years. The median survival times decreased from 57.7 months in very early stage to 1.6 months in terminal stage. Surgical resection offered the best survival benefit for patients in very early, early and even intermediate stages. Transarterial embolisation and conformal radiotherapy offered survival benefits for selected patients in advanced and terminal stages. In conclusion, following the treatment schedules allocated by BCLC staging had survival benefits for HCC patients.

Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma.

The objective of this study was to examine the usefulness of platelet counts in the diagnosis of cirrhosis and for identifying high‐risk individuals in a community‐based hepatocellular carcinoma (HCC) screening program.

Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis

Summary.  We assessed the efficacy of interferon (IFN) alpha‐2b plus ribavirin therapy in patients with hepatitis C virus (HCV)‐related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty‐two HCV‐cirrhotic patients receiving IFN alpha‐2b (3 or 5 MU thrice weekly) and oral ribavirin (1000–1200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan–Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log‐rank test and by multivariate Coxs regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow‐up period of 37 (12–63) months, HCC developed in 11 patients with non‐SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan–Meier method also showed that old age (≥60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Coxs regression analysis, non‐SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha‐2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV‐related cirrhosis.

Clinical Significance of Hepatitis B Virus (HBV) Genotypes and Precore and Core Promoter Mutations Affecting HBV e Antigen Expression in Taiwan

ABSTRACT To assess the prevalence and clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations in Taiwan, a cohort of 200 Taiwanese chronic hepatitis B patients was analyzed. The HBV genotypes and sequences of the precore and the core promoter regions were determined in 66 asymptomatic carriers and 134 patients who had liver biopsy-verified chronic hepatitis and liver cirrhosis. The HBV e-antigen (HBeAg)-negative patients had a higher frequency of mutations at core promoter nucleotides 1753 and 1773 and precore nucleotides 1846, 1896, and 1899 than HBeAg-positive patients. Among the 200 patients, the frequencies of genotype C, T1762 and A1764, C1753, T1766 and A1768, and A1896 mutations increased and the frequencies of T or G1752, T1773, G1799, and C1858 mutations decreased with advancing liver diseases. These factors were different between those with HBeAg-positive status and those with HBeAg-negative status. Based on multiple logistic regression analysis, the risk factors of liver cirrhosis for 200 patients were the presence of T1762 and A1764 mutations (odds ratio [OR] = 11.11; 95% confidence interval [CI] = 3.91 to 31.25; P < 0.001), age ≥35 years (OR = 3.42; 95% CI = 1.33 to 8.77; P = 0.011), and genotype C (OR = 2.87; 95% CI = 1.21 to 6.81; P = 0.017). Further categorical analysis found that 62.1% of patients with genotype C, T1762 and A1764 mutations and age ≥35 years had liver cirrhosis. None of the 55 patients infected with the genotype B, A1762 and G1764 wild type and age <35 years showed liver cirrhosis. In conclusion, our data suggest that pathogenic differences between HBeAg-positive and -negative patients may exist. In Taiwan, HBV genotype C and the T1762 and A1764 mutations may play a role in HBV-related liver cirrhosis, and these could serve as molecular markers for prediction of the clinical outcomes of chronic HBV patients.

Combined Mutations in Pre-S/Surface and Core Promoter/Precore Regions of Hepatitis B Virus Increase the Risk of Hepatocellular Carcinoma: A Case-Control Study

BACKGROUND We sought to investigate the role of sequence variations in pre-S/surface and basal core promoter (BCP)/precore regions of the hepatitis B virus (HBV) in hepatocellular carcinoma (HCC). METHODS The direct sequencing in pre-S/surface and BCP/precore regions of HBV was determined for 80 patients with HCC and 160 control patients with HBV infection. RESULTS Compared with control patients, patients with HCC had higher frequencies of pre-S deletions and amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes; at the start codon in pre-S2 genes; and at codon 68 in surface genes. Patients also had a lower frequency of amino acid substitution at codon 2 in pre-S2 genes, compared with control patients. In BCP/precore regions, patients with HCC had higher frequencies of C or G1753, A1762/T1764, T1846, and A1899. Multivariate analysis showed that pre-S deletions, I68T surface gene, T1762/A1764, and A1899 were independent factors associated with the development of HCC. The HBV strain with a complex mutation pattern rather than a single mutation was associated with HCC, and the HCC risks increased for patients having these factors in combination. CONCLUSIONS Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were independent risk factors for HCC. Combination of these viral mutations appeared to increase the risk of HCC.

Validation of clinical AJCC/UICC TNM staging system for hepatocellular carcinoma: analysis of 5,613 cases from a medical center in southern Taiwan.

This study was aimed to validate the 5th and 6th editions of tumor‐node‐metastasis (TNM) system for patients with hepatocellular carcinoma (HCC), and attempted to improve prognostic stratification by modifying the 6th edition according to vascular invasion and tumor size. From 1986 to 2002, a total of 5,613 HCC cases from Kaohsiung Chang Gung Memorial Hospital in southern Taiwan were enrolled. The 6th edition was modified by dividing stage I into stages IA (single tumor, ≤2cm) and IB (single tumor, >2cm), and by dividing stage II into IIA (multiple tumors, none >5cm) and IIB (tumor with segmental macro vascular invasion). The Akaike information criteria (AIC), within a Cox proportional hazard regression model were used; lower AIC value indicated a better discriminatory ability for staging system. The 1‐, 3‐, 5‐, and 7‐year overall survival rates were 45.6, 25.9, 17.9, and 13.4%, respectively. Significant differences in survival curve existed in the 5th, 6th, and modified 6th edition TNM systems. For the modified 6th edition TNM, survival differed significantly between stages IA and IB, and between stage IIA and IIB. The AIC values of 5th (72,328), 6th (72,188), modified 6th (71,991) edition TNM system were decreasing. This investigation demonstrated better prognostic stratifications for the 6th edition than the 5th edition TNM staging system. Moreover, the modified 6th edition staging system demonstrated better prognostic prediction than the former two. Pretreatment staging and simple classification of current modified 6th edition TNM staging can be applied to all HCC patients and are clinically useful.

Effects of ginger on gastric emptying and motility in healthy humans.

Objective Ginger has been reported to improve upper gastrointestinal symptoms. Little information about the effects of ginger on gastric motor function, exists, however. Our aim was to investigate the effects of ginger on gastric emptying, antral motility, proximal gastric dimensions, and postprandial symptoms. Methods Twenty-four healthy volunteers were studied twice in a randomized double-blind manner. After an 8 h fast, the volunteers ingested three ginger capsules (total 1200 mg) or placebo, followed after 1 h by 500 ml low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires. Data are expressed in terms of mean±standard error. Results Antral area decreased more rapidly (P<0.001) and the gastric half-emptying time was less after ginger than placebo ingestion (13.1±1.1 vs. 26.7±3.1 min, P<0.01), whereas the frequency of antral contractions was greater (P<0.005). Fundus dimensions did not differ, and there was no significant difference in any gastrointestinal symptoms. Conclusion Ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers. These effects could potentially be beneficial in symptomatic patient groups.

Controlled trial of protease inhibitor gabexelate mesilate (FOY) in the treatment of acute pancreatitis.

A controlled trial with synthetic protease inhibitor gabexelate mesilate (FOY) in the treatment of acute pancreatitis was conducted in a total of 42 patients. The age, sex, etiology of pancreatitis, initial serum amylase level, and amylase creatinine clearance ratio were comparable between FOY-treated and control groups. FOY did not alter the course of the disease, but there was a weak trend toward lower morbidity and mortality in the FOY-treated patients. These results may justify further, larger scale studies or evaluation of alternate dosage or route of administration.